Proposed herein is an in vivo study of the transplacental flux of individual amino acids, glucose and lactate in pregnant sheep. The effects of maternal fasting and of maternal hormonal changes which occur during pregnancy or during fasting in transplacental flux of nutrients will be determined and the subsequent effect on fetal growth assessed. The overall goal of this project is an understanding of the mechanisms by which maternal nutrition and endocrine status influence the provision of nutrients to the mammalian fetus to support appropriate growth. The objectives are: 1. to determine whether transplacental flux of amino acids is appreciably influenced by factors which in vitro have been shown to affect uptake of certain amino acids by placenta, i.e., insulin-sensitivity; 2. to ascertain if the decreased uterine blood flow rates and decreased concentrations of glucose and amino acids in maternal blood which occur during fasting result in decreased umbilical uptakes of various substrates, and 5. to determine the relative effects of fetal substrate availability and fetal insulin and somatomedim levels on fetal cartilage growth. Pregnant sheep will be surgically prepared with indwelling catheters in fetal pedal vein and artery, umbilical vein, maternal femoral artery and vein, and a branch of the uterine artery. A blood flow transducer will be placed around the uterine artery of the pregnant horn. This preparation permits manipulation of maternal diet, peripheral and/or uterine hormonal status, and uterine vascular bed substrate concentrations independently. Umbilical blood flow will be determined by the steady state antipyrine diffusion method; uterine blood flow will be measured by flowmeters. Amino acid concentrations will be determined by automated ion-exchange column chromatography, glucose and lactate by enzymatic assays, and serum insulin by radioimmunoassay. Umbilical substrate uptakes will be determined by application of the Fick principle. The effects of dietary and endocrine manipulations on fetal growth will be assessed by rate of sulfate incorporation in the fetal cartilage.